This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Spinal Muscular Atrophy (SMA) is a motor neuron degenerative disease that is one of the most common genetic causes of infant mortality, affecting 1 in 6,000 live births. SMA is caused by reduced levels of the Survival of Motor Neurons protein (SMN), with the severity of the disease determined by the decrease of normal SMN present in the cell.The SMN protein is the core component of a large ribonucleoprotein complex known as the SMN complex, which functions in the assembly of small nuclear ribonucleoproteins (snRNPs) required for pre-mRNA splicing. Of the 25 SMA patient mutations that have been identified, 12 of them have been mapped to the C-terminus of SMN known as the YG box, which is highly conserved across different species. The YG box has been identified as the oligomerization domain because deletions in this region cause SMN to change from a large oligomer to a monomer. We would like to examine the human YG box using x-ray crystallography and biophysical methods to better understand its oligomeric properties and how SMA patient mutations may affect the native oligomerization of this domain.